# US 8,540,969 B2 · Aerosol dispersions of particles with active pharmaceutical ingredients

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- Number: US 8,540,969 B2
- Document ID: US8540969B2
- Status: Granted
- Kind: B2
- Application number: 12/596,508
- Filed: 2008-04-18
- Published: 2010-05-20
- Granted: 2013-09-24
- Earliest claimed: 2007-04-18
- Assignees: Particle Sciences, Inc.
- Applicants: Andrew Loxley; Ismar Dizdarevic; Mark Mitchnick
- Inventors: Andrew Loxley; Ismar Dizdarevic; Mark Mitchnick
- Web page: https://patentgrep.com/patent/US8540969B2

## CPC

- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions}
- A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]}
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/16: Central respiratory analeptics
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 19/00: Drugs for skeletal disorders
- A61P 25/24: Antidepressants
- A61P 33/06: Antimalarials
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Aerosols containing a plurality of aqueous droplets, each droplet containing on average at least one essentially-neutral particle sized to fit within the droplet are provided. Aerosols wherein an active pharmaceutical ingredient is attached to, or otherwise incorporated in the essentially neutral particles are also provided. Methods for administering an active pharmaceutical ingredient to a subject in need thereof via inhalation of these aerosols, preferably via nebulizer, are also provided.

## Claims

### Claim 1

A method for producing an aerosol without requiring a hazardous organic solvent, said method comprising:
heating a solid lipid or wax above its melt temperature to form a molten lipid or wax;
adding an active pharmaceutical ingredient and amphiphile to the molten lipid or wax to form an emulsion;
forming submicron particles using high shear in the emulsion; and
cooling the emulsion and particles to room temperature to form the aerosol, wherein the aerosol comprises a plurality of aqueous droplets, each aqueous droplet of said plurality comprising:
an essentially neutral colloidal particle sized to fit inside the droplet, wherein the essentially neutral particle is selected from the group consisting of a polymer, a solid lipid, a natural or synthetic wax, a pharmaceutically acceptable oil, a micelle, a polymersome, a vesicle, a polyplex, a coacervate and an inorganic particle; and
an active pharmaceutical agent incorporated within the essentially neutral particle or attached to a surface of the essentially neutral particle.

### Claim 2 (depends on 1)

The method of claim 1 wherein the aerosol of aqueous droplets is produced by a nebulizer.

### Claim 3 (depends on 1)

The method of claim 1 wherein the aerosol of aqueous droplets is produced by a metered dose inhaler.

### Claim 4 (depends on 1)

The method of claim 1 wherein the aerosol of aqueous droplets is produced by an aerosol generating device.

### Claim 5 (depends on 1)

The method of claim 1 wherein the aqueous droplets have a mean droplet size of 50 microns in diameter or less.

### Claim 6 (depends on 5)

The method of claim 5 wherein the mean droplet size is less than 10 microns.

### Claim 7 (depends on 5)

The method of claim 5 wherein the mean droplet size is 1 to 5 microns.

### Claim 8 (depends on 1)

The method of claim 1 wherein the essentially neutral particle is stabilized by an amphiphile.

### Claim 9 (depends on 8)

The method of claim 8 wherein the amphiphile is a surfactant, a polymeric stabilizer or a finely divided solid having a contact angle against a solution in which the particles are dispersed in, that is around 90 degrees so that it sits at the interface between the particle and the liquid.

### Claim 10 (depends on 1)

The method of claim 1 wherein the active pharmaceutical agent is incorporated within the essentially neutral particle.

### Claim 11 (depends on 1)

The method of claim 1 wherein the active pharmaceutical agent is attached to a surface of the essentially neutral particle.

### Claim 12 (depends on 1)

A method for delivering an active pharmaceutical agent to the pulmonary system of a subject in need of the active pharmaceutical agent comprising administering to the subject via inhalation an aerosol produced by the method of claim 1.

### Claim 13 (depends on 12)

The method of claim 12 wherein the aerosol is administered via a device that can produce an aerosol with an average droplet size between 1-10 microns.

### Claim 14 (depends on 13)

The method of claim 13 wherein the device is a nebulizer.

### Claim 15 (depends on 13)

The method of claim 13 wherein the device is a metered dose inhaler.